1. Field of the Invention
The present invention relates to the field of glaucoma diagnosis and treatment. More specifically, the present invention provides methods for diagnosis of glaucoma by measuring the amount of GRβ present in the trabecular meshwork of a patient's eye.
2. Description of the Related Art
Glaucoma is usually diagnosed by monitoring a patient's visual field loss, changes in the appearance of their optic disc, and their intraocular pressure. Glaucoma is currently treated using one or more of three strategies to lower the elevated intraocular pressure associated with the disease: with pharmaceuticals (such as beta-blockers, carbonic anhydrase inhibitors, miotics or prostaglandins), with laser trabeculoplasty, and/or with glaucoma filtration surgery. All of these therapies indirectly lower intraocular pressure but do not address the underlying disease process occurring in the trabecular meshwork. It would be advantageous to be able to diagnose glaucoma before a patient begins experiencing a loss in their visual field and deterioration of their optic disc.
There is a large body of evidence suggesting that glucocorticoids are involved in the generation of ocular hypertension and glaucoma (Clark 1995). The human glucocorticoid receptor (hGR) and its isoforms, hGRα (SEQ ID NO:3) and hGRβ (SEQ ID NO:1), are described in Encio and Detera-Wadleigh (1991) (See also FIG. 1). Several investigators have shown that the human trabecular meshwork (TM) contains the classical glucocorticoid receptor (hGRα) (Weinreb et al. 1981; Hernandez et al. 1983). Recently, the expression of an alternatively spliced form of the human glucocorticoid receptor (hGRβ) was discovered in non-ocular tissues and cells (Bamberger et al. 1995; Oakley et al. 1996). This alternatively spliced form of hGR is expressed as a protein (SEQ ID NO:2) which no longer binds glucocorticoids, but is able to interfere with the activated form of the normal glucocorticoid receptor and block or alter physiological functions of the glucocorticoid receptor.